This proposal describes a research program directed towards the total synthesis of azaspiracids-l, -2, -3, and -6, and fragments thereof, for biological and analytical purposes. Isolated from the mussel Mytilus edulis, these marine neurotoxins are the causative agents of seafood poisoning in humans and tumorogenesis in rats. These extremely scarce biotoxins have been isolated only in minute quantities and it remains for chemical synthesis to render them available for the acutely needed analytical work to detect and quantify them in seafood before releasing it for human consumption. Considerable progress has been made already by this group, uniquely positioning us to accomplish the efficient total synthesis of all four azaspiracids, develop antibodies against them, and investigate their mechanism of action and full spectrum of biological properties. The latter investigations will be carried out in collaboration with biology experts and are expected to result, in particular, in the development (through antibody production) of a bioassay for the determination of the toxins. The significance of the proposed work lies primarily in improving and assuring environmental health, detecting and measuring marine biotoxins, and cleaning the oceans, as well as to prevent seafood poisoning in humans that may include both short (e.g. nausea, vomiting, severe diarrhea and stomach cramps) and long term (e.g. lung, liver, spleen and lymphocyte damage as well as cancer) health hazards. The project is also expected to advance our knowledge in chemical synthesis and impact favorably the drug discovery and development process.